Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the viral family Arteriviridae, causes respiratory disease in growing swine and fetal mortality. Efforts to contain this virus have included early diagnosis, enhanced bio security measures, herd management and application of vaccines (Holtkamp et al., 2013. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. Journal of Swine Health and Production 21, 72-84; Pileri and Mateu, 2016. Review on the transmission porcine reproductive and respiratory syndrome virus between pigs and farms and impact on vaccination. Vet. Res. 47, 108). However, the available modified live vaccines (MLV) only provide partial protection against heterologous viruses and are dwarfed by the number of PRRSV strains circulating worldwide. PRRSV strains vary greatly and each exists as one of two genetically different types (Type 1 and 2). Each genotype continues to evolve by both imprecise replication due to its inherent polymerase error rate and by recombination (Hanada et al., 2005. The origin and evolution of porcine reproductive and respiratory syndrome viruses. Mol. Biol. Evol. 22, 1024-1031; Kappes and Faaberg, 2015. PRRSV structure, replication and recombination: Origin of phenotype and genotype diversity. Virology 479-480, 475-486; Shi et al., 2013. Recombination is associated with an outbreak of novel highly pathogenic porcine reproductive and respiratory syndrome viruses in China. J. Virol. 87, 10904-10907; Shi et al., 2010. Molecular epidemiology of PRRSV: a phylogenetic perspective. Virus Res. 154, 7-17). The swine industry is also hampered by the lack of a vaccine that effectively differentiates infected from vaccinated animals (DIVA).
In PRRSV infected cells, the nsp2 protein not only is present as a full-length protein but is processed into variably sized isomers (Wang, et al., 2008. Attenuation of porcine reproductive and respiratory syndrome virus strain MN184 using chimeric construction with vaccine sequence. Virology 371, 418-429; Yuan, et al., 2000. Heteroclite subgenomic RNAs are produced in porcine reproductive and respiratory syndrome virus infection. Virology 275, 158-169; Yuan, et al., 2004. Characterization of heteroclite subgenomic RNAs associated with PRRSV infection. Virus Res. 105, 75-87.
Ingelvac PRRS® MLV (MLV) is used widely in several countries to dampen the effect of PRRSV herd infection in young pigs, has been used safely for 20 years with few instances of reversion to virulence, replicates sufficiently in vaccinated swine and is a low cost platform that is affordable for the industry (Botner et al., 1997. Appearance of acute PRRS-like symptoms in sow herds after vaccination with a modified live PRRS vaccine. Vet. Rec. 141, 497-499; Jeong et al., 2016. Evaluation of a 20 year old porcine reproductive and respiratory syndrome (PRRS) modified live vaccine (Ingelvac((R)) PRRS MLV) against two recent type 2 PRRS virus isolates in South Korea. Vet. Microbiol. 192, 102-109; Martinez-Lobo et al., 2013. Safety of Porcine Reproductive and Respiratory Syndrome Modified Live Virus (MLV) vaccine strains in a young pig infection model. Vet. Res. 44, 115; Mengeling et al., 1999. Identification and clinical assessment of suspected vaccine-related field strains of porcine reproductive and respiratory syndrome virus. Am. J. Vet. Res. 60, 334-340; Nielsen et al., 2001. Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations. J. Gen. Virol. 82, 1263-1272). Type 2 strain VR-2332, the parent of MLV, causes a mild disease under defined conditions, thus concerns of simple reversion to virulence are reduced. Moreover, VR-2332 replicates at a lower rate in swine and does not result in a reduction in weight gain when compared to more pathogenic isolates (Guo et al., 2013. Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology 435, 372-384; Guo et al., 2013. Chinese and Vietnamese strains of HP-PRRSV cause different pathogenic outcomes in United States high health swine. Virology 446, 238-250).
All of the references cited herein, including U.S. Patents and U.S. Patent Application Publications, are incorporated by reference in their entirety.